This invention relates to improved solvent systems, and in particular to a solvent system for use in the production of bisphosphonate compounds.
Bisphosphonate compounds have generally been made by the reaction of carbonyl compounds with phosphorus halides. It is known in the art to use a variety of different carriers/solvents in the production of bisphosphonate compounds. However, all of the carriers/solvents used to date demonstrate major disadvantages, as to their use.
It is known from U.S. Pat. No. 4,407,761 to use chlorobenzene to attempt to solubilize the reaction. However, this method generates a high amount of an amorphous orange solid termed “orange pyrophoric solid” containing phosphorus and oxidised phosphorus. Orange pyrophoric solid is difficult to handle and as such is an undesirable by-product.
It is known from WO 98/34940 to use long chain glycols as carriers/solvents, to attempt to stop, the aforementioned solidification. However, solidification of the reaction still occurs and the long chain glycols cannot be recycled as they have been converted to chloride derivatives.
It is also known from U.S. Pat. No. 5,019,651 to use methane sulphonic acid as a carrier/solvent to overcome the aforementioned solubility difficulties. However, orange pyrophoric solid is again formed and the methane sulphonic acid cannot be recycled as it has been converted into methane sulphonyl chloride.
It is, therefore, desirable in the production of bisphosphonates to provide a carrier/solvent which does not lead to the formation of orange pyrophoric solid, which can be recycled and which does not cause solidification of the reaction.